1. Pharmacologic and Nonpharmacologic Treatments of Atrial Fibrillation
Martha Drake MS, FNP-BC
Chicago Heart and Vascular Consultants, LTD
Purdue Northwest Doctorate of Nursing Program

2. Learning Objectives
Discuss the incidence of atrial fibrillation (AF) in the population
Discuss and summarize the pharmacologic and nonpharmacologic treatment options for atrial fibrillation (AF)
Discuss ChadVasc score and how it is utilized
Discuss the financial burden and risk factors of AF
Distinguish the difference in treatment plans of the symptomatic versus asymptomatic patient in AF
Recognize the potential symptoms of a patient in AF

3. Facts About AF https://www. cdc
An estimated 2.7–6.1 million people in the United States have AF
Approximately 2% of people younger than age 65 have AF, while about 9% of people aged 65 years or older have AF.
African Americans are less likely than those of European descent to have AF.
Many people diagnosed with AF are asymptomatic and it is identified they have AF during routine physicals

4. Risks and Costs….. The risk for AF increases with age.
High blood pressure, which also increases in risk with advancing age, accounts for 14% to 22% of AFib cases.
More than 750,000 hospitalizations occur each year because of AF
AF contributes to an estimated 130,000 deaths each year..
AFib costs the United States about $6 billion each year.
Medical costs for people who have AF are about $8,705 higher per year than for people who do not. have AF

6. Mechanisms Under Investigation
Atrial fibrillation (AF) affects your heart’s ability to pump blood effectively and causes blood to pool in an area of the heart called the left atrial appendage (LAA).
Clots forms at the LAA When a blood clot escapes from the LAA and can travel to the brain and cause a stroke.
Neurohumoral cascade activation
Catecholamine excess
Hemodynamic stress
Atrial ischemia
Atrial inflammation
Metabolic stress

9. Risk Factors https://www. cdc
Advancing age
High blood pressure
Obesity
European ancestry
Diabetes
Heart failure
Ischemic heart disease
Hyperthyroidism
Chronic kidney disease
Heavy alcohol use
Enlargement of the chambers on the left side of the heart

13. AF Categories http://emedicine.medscape.com/article/151066-overview
First documented episode (new onset)
Recurrent atrial fibrillation: after two or more episodes.
Paroxysmal atrial fibrillation: if recurrent atrial fibrillation spontaneously converts to sinus rhythm.
Persisting atrial fibrillation: if an episode of atrial fibrillation persists more than 7 days.
Permanent atrial fibrillation: if atrial fibrillation persists after an effort of electrical or chemical cardioversion
Lone AF is atrial fibrillation in patients younger than 60 years in whom no clinical or electrocardiographic signs of heart or lung disease are present. These patients have a good prognosis regarding thrombo-embolic events.
Non-valvular atrial fibrillation is atrial fibrillation in patients without heart valve disease or heart valve replacement or repair.

14. Symptomatic Versus Asymptomatic

15. The Symptomatic Patient
Palpitations
Dyspnea
Fatigue
Dizziness
Chest pain
Signs of decompensated heart failure
Hemodynamically unstable
Tachycardia-induced cardiomyopathy
Systemic Thromboembolism

16. Pharmacologic Treatments

17. Tools To Help Determines Whether The Patient Receives Anticoagulation
ATRIA Tool:
The ATRIA risk scoring scheme can be used to help guide the decision for warfarin therapy in patients in need of anticoagulation.
The ATRIA risk scoring scheme may be used as one potential tool to stratify the risk of major hemorrhage in patients in whom warfarin anticoagulation is being considered.
CHADS2 and CHA2DS2-VASc
The CHADS2 score is one of several risk stratification schema that can help determine the 1 year risk of an ischemic stroke in a non- anticoagulated patient with non-valvular AF
CHA2DS2-VASc : this score takes into account other stroke risk factors and may be able to accurately identify which patients are at low enough stroke risk to forgo oral anticoagulation.
fibrillation-stroke-risk

18. CHA2DS2-VASc Score if present Congestive Heart Failure 1 Hypertension
Age ≥ 75 years 2
Age between 65 and 74 years
Stroke/TIA/TE
Vascular disease (previous MI, peripheral arterial disease or aortic plaque)
Diabetes mellitus
Female

19. Anticoagulation Therapy Considerations
Anticoagulation guidelines based on the CHADS2-Vasc score are shown below:
Score
Risk
Anticoagulation Therapy
Considerations
Low
No antithrombotic therapy (or Aspirin)
No antithrombotic therapy (or Aspirin mg daily) 1
Moderate
Oral anticoagulation (or aspirin)
Warfarin INR to , or one of the new oral anticoagulation drugs or aspirin 75mg-325mg daily
2 or greater
High
Oral anticoagulation
Warfarin INR to , or one of the new oral anticoagulation drugs

20. Female, Hypertension, Age 65 or >
Stroke risk was 3.2% per year in >90,000 patients and 4.6% risk of stroke/TIA/systemic embolism. -a 0 score is “low” risk and may not require anticoagulation; -a 1 score is “low-moderate” risk and should consider antiplatelet or anticoagulation, -A score 2 or greater is “moderate-high” risk and should otherwise be an anticoagulation candidate.
CHA2DS2-VASc 3:
Female, Hypertension, Age 65 or >

21. Choices for Anticoagulation
Newer oral anticoagulants (NOACs) that have been approved by the US Food and Drug Administration (FDA) and may be considered as alternatives to warfarin include the following:
Dabigatran (Pradaxa)(direct thrombin inhibitor)
Rivaroxaban (Xarelto)(highly selective direct factor Xa inhibitor)
Apixaban (Eliquis)(factor Xa inhibitor)
Coumadin (Warfarin)

22. Warfarin (Coumadin) Slow onset Dosing is unpredictable
Diet restrictions
Drug interactions (210 Major):
Amiodarone, Biaxin, Amoxicillin, Lansoprazole, NSAIDs, Bactrim, Cipro, Flagyl…Almost all antibiotics
PT/INR checks
“Rat Poison”
Warfarin Resistance
Cost effective option
Reversal Agent: Vitamin K
Should not be crushed
Take with or without food

23. Dabigatran (Pradaxa): Nonvalvular AF for Stroke Prevention
Direct thrombin Inhibitor
Inhibits platelet aggregation
Inhibits tissue factor-induced thrombin generation
Renally excreted; costly
Reversal agent: Idarucizumab (Praxbind) (October, 2015)
Dosing: CrCl > mg po BID
CrCl 15-30: 75mg po BID
CrCl < 15 or on dialysis; not recommended
FYI; not for DVT, PE, Mech Heart Valves or for prophylaxis for knee or hip replacements

24. Rivaroxaban (Xarelto)
Factor Xa Inhibitor
Daily dosing versus BID
Dosing is 20mg po daily for CrCl >50
Dosing 15mg po daily for CrCl 15-50
May be crushed
Should be stopped 24 hour prior to any surgical procedure
8/8/16: the FDA did not approve the antidote
Expensive
Can be used for DVT, PE, Hip/knee replacement prophylaxis
NSAIDS
Should be taken with food at 15-20mg dose; not with 10mg dose

25. Apixaban (Eliquis) Dosing: 5mg po BID
In patients with 2 of the following:
>80 years; body weight less than 60kg (132#), or serum Cr >1.5 dosing is 2.5mg p BID
Not for PE, DVT, Heart Valves
Stop 48 hours prior to surgery
No dose adjustment for mild hepatic impairment
Not recommended for severe hepatic impairment
May be crushed
No antidote: 8/8/16 FDA did not approve antidote

26. Switching Agents
Eliquis: if switching from Warfarin to Eliquis, stop Warfarin and start Eliquis when INR is less than 2.0
Eliquis to Warfarin: Stop Eliquis and then start Warfarin the next day at same time the Eliquis was taken
Xarelto: if switching from Warfarin to Xarelto, stop Warfarin and start Xarelto when INR < 3
Xarelto to Warfarin: Stop Xarelto and then next day start Warfarin at same time Xarelto should have been given

27. Switching Agents Continued
Warfarin to Pradaxa: stop warfarin and start Pradaxa when the INR is less than 2
Pradaxa to Warfarin:
CrCl >50: start Warfarin 3 days before stopping Pradaxa
Cr Cl 30-50: start Warfarin 2 days prior to stopping Pradaxa
Cr Cl: ; start Warfarin 1 day before stopping Pradaxa
Cr Cl <15; no recommendations can be made

28. Factors That Can Cause Bleeding with Warfarin Therapy
History of bleeding (the strongest predictive risk factor)
Age older than 75 years
Liver or renal disease
Malignancy
Thrombocytopenia or aspirin use
Hypertension
Diabetes mellitus
Anemia
Prior stroke
Fall risk
Genetic predisposition
Supratherapeutic INR

29. Can anticoagulation be stopped after return to sinus rhythm in patients on antiarrhythmic drugs?
There is currently no data to support the assertion that patients in sinus rhythm on antiarrhythmic treatment have a low risk of thromboembolism/stroke.
Even patients with significant symptoms from AF can have significant asymptomatic episodes. In patients treated with antiarrhythmic drugs, the decision to use antiarrhythmic drugs should be independent of the decision to use anticoagulation. Even if apparent sinus rhythm is maintained, anticoagulation should be continued based on the CHADS2 or CHADS2-Vasc score.

30. Key to interpretation of practice guidelines
Agency for Healthcare Research and Quality:
Key to interpretation of practice guidelines Agency for Healthcare Research and Quality: A:
There is good research-based evidence to support the recommendation. B:
There is fair research-based evidence to support the recommendation. C:
The recommendation is based on expert opinion and panel consensus.

31. 2014 ACC Guidelines for AF to Prevent Thromboembolism http://www
For patients with AF or atrial flutter of 48 hours’ duration or longer, or when the duration of AF is unknown, anticoagulation with warfarin (INR 2.0 to 3.0) is recommended for at least 3 weeks before and 4 weeks after cardioversion, regardless of the CHA2DS2- VASc score and the method (electrical or pharmacological) used to restore sinus rhythm (Level of Evidence: B)
For patients with AF or atrial flutter of more than 48 hours’ duration or unknown duration that requires immediate cardioversion for hemodynamic instability, anticoagulation should be initiated as soon as possible and continued for at least 4 weeks after cardioversion unless contraindicated. (Level of Evidence: C)
For patients with AF or atrial flutter of less than 48 hours’ duration and with high risk of stroke, intravenous heparin or LMWH, or administration of a factor Xa or direct thrombin inhibitor, is recommended as soon as possible before or immediately after cardioversion, followed by long-term anticoagulation therapy. (Level of Evidence: C)
Following cardioversion for AF of any duration, the decision about long-term anticoagulation therapy should be based on the thromboembolic risk profile. (Level of Evidence: C)

32. Continued
For patients with AF or atrial flutter of 48 hours’ duration or longer or of unknown duration who have not been anticoagulated for the preceding 3 weeks, it is reasonable to perform transesophageal echocardiography before cardioversion and proceed with cardioversion if no left atrial thrombus is identified, including in the left atrial appendage, provided that anticoagulation is achieved before transesophageal echocardiography and maintained after cardioversion for at least 4 weeks. (Level of Evidence: B)
 For patients with AF or atrial flutter of 48 hours’ duration or longer or when duration of AF is unknown, anticoagulation with dabigatran, rivaroxaban, or apixaban is reasonable for at least 3 weeks before and 4 weeks after cardioversion. (Level of Evidence: C)

33. Management Rate Control Rhythm Control Anticoagulation
Degree of symptoms
Direct Current Cardioversion (DCCV)
Transesophageal Echocardiogram (TEE) Cardioversion
Presence of comorbidities
Candidacy for AF ablation

34. Agents Used for AF Rate Control Rhythm Control
Beta-blockers (Metoprolol tartrate)
Calcium channel blockers (Diltiazem)
Digoxin (Lanoxin)
Amiodarone (Cordarone)
Flecainide (Tambacor)
Propafenone (Rhythmol)
Dofetilide (Tikosyn)
Amiodarone (Cordarone)
Dronedarone (Multaq)
Sotalol (Betapace)

35. Beta-Blockers Metoprolol Tartrate 25mg100mg PO BID
Metoprolol Succinate mg po daily
Atenolol mg po daily
Propanolol 10-40mg o TID to QID
Nadolol mg po daily
Carvedilol mg po BID
Bisoprolol mg po daily

36. Nondihydropyridine calcium channel antagonists
Verapamil 180–480 mg QD (ER)
Diltiazem 120–360 mg QD (ER)

37. Digitalis Glycosides/Amiodarone
Digitalis glycosides: 0.125–0.25 mg QD
Amio dosing can vary

38. Pharmacologic Cardioversion http://www. onlinejacc
Flecainide, dofetilide, propafenone, and IV ibutilide are useful for cardioversion of AF or atrial flutter
Amiodarone is reasonable for pharmacological cardioversion of AF
 Propafenone or flecainide (“pill- in-the-pocket”) to terminate AF out of hospital is reasonable once observed to be safe in a monitored setting
Dofetilide should not be initiated out of hospital

39. Nonpharmacologic Treatments

40. Direct Current Cardioversion (DCCV)
Cardioversion is recommended for AF or atrial flutter to restore sinus rhythm. If unsuccessful, cardioversion attempts may be repeated.
Cardioversion is recommended for AF or atrial flutter with RVR, that does not respond to pharmacological therapies
Cardioversion is recommended for AF or atrial flutter and pre-excitation with hemodynamic instability
It is reasonable to repeat cardioversion in persistent AF when sinus rhythm can be maintained for a clinically meaningful time period between procedures

41. Transesophageal Echocardiogram (TEE)
TEE-guided cardioversion may be a better option than conventional therapy in certain patients, such as those who are highly symptomatic, hemodynamically compromised, newly diagnosed with AF, or have a high risk of stroke.

42. Catheter Ablation
AF catheter ablation is reasonable for some patients with symptomatic persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication(Level of Evidence: A)

43. Catheter Ablation Wann LS, Curtis AB, January CT, et al
Catheter Ablation Wann LS, Curtis AB, January CT, et al ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation Jan (1):
Catheter ablation performed in experienced centers is recommended in the 2011 update to the ACCF/AHA/HRS AF guidelines for the following indications:
It is recommended as an alternative to pharmacologic therapy to prevent recurrent paroxysmal AF in significantly symptomatic patients with little or no structural heart disease or severe pulmonary disease 
It is reasonable as a treatment for symptomatic persistent AF
It may be reasonable as a treatment for symptomatic paroxysmal AF in patients with some structural heart disease

44. The WATCHMAN Procedure https://www. fda
WATCHMAN is a one-time implant that doesn’t have to be replaced and can’t be seen outside the body. It’s about the size of a quarter and made from very light and compact materials commonly used in many other medical implants.
The WATCHMAN into the left atrial appendage (is inserted into the LAA of your heart.
The procedure is done under general anesthesia and takes about an hour. Patients commonly stay in the hospital overnight and leave the next day.

45. Inclusion Criteria https://www. fda
The WATCHMAN should only be used in patients who:
 Have atrial fibrillation not related to heart valve disease.
Are at increased risk for a stroke.
Are recommended for anticoagulation
Are suitable for warfarin (Coumadin) therapy.
Have an appropriate reason to seek a non-drug alternative to warfarin.

46. Post WATCHMAN
Warfarin is taken for approximately for 45 days or until the LAA is permanently closed off.
Clopidogrel and aspirin are taken for 6 months.
Aspirin is taken long-term.

47. Indications for Future Research
It is evident that future studies are needed to better inform clinicians about the risks and benefits of therapeutic options for an individual patient.
Continued research is needed into the mechanisms that initiate and sustain AF. A better understanding of causes of AF at the cellular level is important to future research
New pharmacological options in the antiarrhythmic drug category are needed to target the atria.
Further investigations and strategies should focus on:
AF, AF burden, and stroke risk
Reversing the growing epidemic of AF
Genetic, epidemiological, and clinical studies.

48. Thank You! Questions/Comment???????????????????